During his professional career, Cambiasso has won 23 official titles (as of the end of 2011), being the Argentine footballer with most honours in history, one more than Alfredo Di Stéfano.[2] The majority of his titles were won during his ten seasons at Inter Milan, including five Scudetti and the 2010 Champions League.

In July 2004, Cambiasso signed with Inter Milan after his contract with Real Madrid expired in June.[3] He helped Inter Milan win the Coppa Italia in his first season with the club,[4] playing regularly as a defensive midfielder, partnered in the middle of Inter's midfield with fellow Argentine Juan Sebastián Verón. In Italy, he became known as one of the outstanding players of the 2004–05 season, along with Milan's Kaká.

During the return match for the final of the 2006 Coppa Italia, Cambiasso scored an impressive goal, the first of the match, for the 3–1 victory over Roma.[5] On 9 September 2006, he scored twice in the opening game of the season, with Inter defeating Fiorentina 3–2. On 7 November 2007, he along with Zlatan Ibrahimović scored a brace apiece to defeat CSKA Moscow 4–2 in the Champions League.[6] On 23 December, Cambiasso netted the winning goal for Inter as they came from behind to defeat city rivals Milan 2–1 in the Derby della Madonnina.[7]

On 23 March 2009, it was announced that Inter and Cambiasso had come to terms about a contract renewal, extending his contract at the club until 2014.[8] He was very important in the 2009–10 UEFA Champions League win as well, scoring the second goal of a 2–1 victory over Chelsea at the San Siro,[9] a result which ultimately helped Inter go on to win the final, 2–0, against Bayern Munich on 22 May 2010.[10] In a Champions League match against FC Twente on 24 November, Cambiasso scored the game's only goal, securing a place in the knockout round for the holders.[11] On 9 January 2011, Cambiasso scored twice as Inter came from a goal down to defeat Catania 2–1.[12]

Cambiasso received the first red card of his Inter career on 30 March 2013 for a reckless tackle on Sebastian Giovinco; he was suspended for one match.[13] On 22 September 2013, Cambiasso scored Inter's sixth goal in their 7–0 hammering of newly promoted club Sassuolo.[14] Four days later, Cambiasso helped Inter come from a goal down at home to Fiorentina, scoring Inter's first goal in their 2–1 victory.

At the end of the 2013–14 season, Cambiasso left Inter as his contract expired and he was not offered an extension. Technical director Piero Ausilio said "He waited for our decision until now, and for that he must be thanked, but I'm convinced that in his future he'll have a role at Inter".[15]

On 28 August 2014, Cambiasso signed a one-year deal with newly promoted Leicester City, joining on a free transfer, having been released by Inter Milan following the 2013–14 season.[16][17] In his first interview since joining the club, Cambiasso cited the club's desperate pursuit of him and the lure of Premier League football as the reasons he signed.[18] He was called up for his first game three days after signing, a 1–1 draw at the King Power Stadium against Arsenal, as an unused substitute.[19] Cambiasso made his debut for Leicester on 13 September against Stoke City, coming on as a half-time substitute and impressing in the club's 1–0 win, their first of the league season.[20] His first goal was an equaliser as Leicester beat Manchester United 5–3 at home after trailing 1–3 with 30 minutes to play.[21] Cambiasso scored his second goal of the season, an opener in 4th minute following an assist from Leonardo Ulloa, in a 3–2 loss against Queens Park Rangers at Loftus Road.[22] That was Leicester's first goal 504 minutes without scoring, or 56 days.[23][24]

Cambiasso made his senior national debut in 2000 for Argentina. He participated in the 2005 FIFA Confederations Cup with his national side, a tournament in which Argentina reached the final. On 15 May 2006, he was named in the Argentine national team for the 2006 World Cup.[25] On 16 June, he capped a 24-pass Argentine interplay with a finish to score the second goal in a 6–0 victory over Serbia and Montenegro.[26] In the quarter-finals match against Germany on 30 June 2006, the match went into penalties, where Cambiasso had his penalty kick saved, resulting in Argentina losing 4–2 and Germany progressing to the semi-final.[27] The following year, he represented his country at the 2007 Copa América, where Argentina reached the final, losing out to South American rivals Brazil.

Since Diego Maradona took over as Argentina coach, Cambiasso was only called-up once to the national team for a friendly game on 14 November 2009 against Spain,[28] despite continuing to play a vital role for Inter in their treble-winning season, and re-affirming his status as one of Europe's best central midfielders. On 12 May 2010, Cambiasso and Inter teammate Javier Zanetti were controversially left out of the 30-man provisional 2010 World Cup squad for Argentina.[29]

On 20 August 2010, new Argentina coach Sergio Batista recalled Esteban Cambiasso to the national team for the friendly against newly crowned world champions Spain. Argentina handed Spain their first defeat since becoming world champions two months prior, earning a resounding 4–1 win in a friendly at the Monumental Stadium in Buenos Aires.[30] Cambiasso also played for Argentina in the 2011 Copa América on home soil, where they were eliminated by eventual champions Uruguay, on penalties, in the quarter-finals.

Cambiasso is a complete, versatile, consistent, and modern footballer, who possesses acute tactical intelligence, and who is capable of playing in several midfield and defensive positions; although predominantly a central or defensive midfielder, he has also been deployed as a playmaking sweeper on occasion.[36] A strong, left footed player, he is gifted with stamina, good technique, passing range and vision, attributes which allow him to distribute the ball and create chances for team mates.[37][38] In his prime, he was also a quick and hardworking player who was effective defensively thanks to his strong tackling ability; after winning back possession, he was also capable of then initiating attacking plays.[39][40][41][42]

Eurosport said about Cambiasso, when José Mourinho was still managing Inter, "There is nothing glamorous about the bald Argentine, but he is the heartbeat of the Inter side that have become the dominant force in Italian football. Just the kind of determined, hard-running midfielder José Mourinho loves. Originally a destroyer, the 29-year-old has become increasingly adventurous from an offensive standpoint, and weighs in with six to eight goals per season.[43]

Goal.com said, "All in all, this player is one of the greatest players to have ever pulled an Inter shirt on and to grace the pitch in the Serie A. He is an intelligent midfielder, who has the capacity to change the shape of a game off his own boot. He is one of the most influential midfielders in Italian football, and for that reason and many more, he will certainly be remembered as one of the most talented players of all time."[44]

Cambiasso was once married and still is but no longer has any contact with his ex-wife.[citation needed] On 22 November 2008, his ex-wife gave birth to their daughter Victoria before Cambiasso's match against Juventus.[45] After Inter won the Derby d'Italia, Cambiasso dedicated the win to his daughter.[46]

Like other Argentine footballers who share an Italian ancestry, Cambiasso also holds an Italian passport, due to his descent from Serra Riccò (GE), in Liguria, where his great-great-grandfather Francesco Cambiaso emigrated from in the 19th century.[47] Among the early family members who settled in Argentina, his ancestor Antonio Cambiaso was the founder of Buenos Aires' Villa del Parque district in 1908.[48]